Design and optimization of a linker for fusion protein construction .pdf

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1、Availableonlineatwww.sciencedirect.comProgressinNaturalScience19(2009)1197–1200www.elsevier.com/locate/pnscReviewDesignandoptimizationofalinkerforfusionproteinconstructiona,*bacbJianhuaZhang,JunYun,ZhigangShang,XiaohuiZhang,BorongPanaDepartmentofBiomedicalEngineering,Zhe

2、ngzhouUniversity,Zhengzhou450001,ChinabDepartmentofGeneralSurgery,XijingHospital,FourthMilitaryMedicalUniversity,Xi’an710033,ChinacCollegeofMedicine,UniversityofSouthFlorida,FL33647,USAReceived23November2008;receivedinrevisedform9December2008;accepted14December2008Abstra

3、ctBivalent,bispecificsingle-chainantibodyfusionproteinconstructionappearstobeapromisingtoolfortumortherapy.Oneofitsdrawbacksisthatthefunctionandactivityofthefusionproteinshavevariedaffinityand/oranti-tumoractivitycomparedwiththeori-ginalmoleculesfromwhichtheyarederived.Amor

4、eoptimizedlinkerforfusionproteinswouldconfermorefavorablebiologicalactiv-itiesuponbispecificsingle-chainantibodies.Thus,itiscriticaltodesignandoptimizeaninter-peptidelinker.Withdifferentfunctionaldomainsandoptimizedlinkers,fusionproteinsprovideasolidbasefortargetedimmuneth

5、erapyformalignancies.Inthispaper,wereviewtheinter-peptidelinkerstudiesandthedesignofanoptimizedlinkerusinggeneticalgorithms.Thespatialstructureofthefusionproteincanbepredictedbyusinggeneticandbioinformaticsresearch.Basedoncurrentresearch,thefuturefocuswillbeondifferentcor

6、relationmodelstoperformsimulationsofspatialstructuresanddrugmoleculedesign.Ó2009NationalNaturalScienceFoundationofChinaandChineseAcademyofSciences.PublishedbyElsevierLimitedandScienceinChinaPress.Allrightsreserved.Keywords:Homologymodeling;Improvedgeneticalgorithm;Single

7、-chainbispecificantibody;Designofinter-peptidelinker1.Introductionpies.Theseproblemsarecurrentlybeingfacedintumorgenetherapyandarethefocusoffutureresearch.Withthedevelopmentofmolecularbiology,tumorther-Single-chainFvantibodies(forexample,ScFv)areidealapyhasenteredaneraofm

8、oleculeandgenetherapy[1–3].toolsforconstructionofsingle-chainbispecificantibodyThecombinationofgenethera